Department of Radiotherapy, The First Hospital Hospital of China Medical University, Shenyang, China.
Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
J Cell Biochem. 2019 Sep;120(9):14916-14927. doi: 10.1002/jcb.28754. Epub 2019 Apr 23.
To identify an immune-related long noncoding RNA (lncRNA) signature with potential prognostic value for patients with pancreatic cancer.
Pancreatic cancer samples with available clinical information and whole genomic mRNA expression data obtained from The Cancer Genome Atlas (TCGA) were enrolled in our research. The immune score of each sample was calculated according to the expression level of immune-related genes and used to identify the most promising immune-related lncRNAs. According to the risk score developed from screened immune-related lncRNAs, the high- and low-risk groups were separated on the basis of the median risk score. The prediction reliability was further evaluated in the validation set and combination set. Both gene set enrichment analysis (GSEA) and principal component analysis (PCA) were performed for functional annotation, and the microenvironment cell population record was applied to evaluate the immune composition and purity of the tumor.
A cohort of 176 samples was included in this study. A total of 163 immune-related lncRNAs were collected according to Pearson correlation analyses between immune score and lncRNA expression |R| > 0.5, P < 0.01). Nine immune-related lncRNAs (AL138966.2, AL133520.1, AC142472.1, AC127024.5, AC116913.1, AC083880.1, AC124016.1, AC008443.5, and AC092171.5) with the most significant prognostic values (P < 0.01) were identified. In the training set, it was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group (P < 0.001); meanwhile, similar results were found in the validation set, combination set and various stratified sets (P < 0.05, P < 0.001, P < 0.05, respectively). Moreover, the signature was identified as an independent prognostic factor and significantly associated with the OS of pancreatic cancer. The area under curve (AUC) of the receiver operating characteristic curve (ROC curve) for the nine lncRNA signature in predicting the 2-year survival rate was 0.703. In addition, the low-risk and high-risk groups displayed different distributed patterns in PCA and different immune statuses in the GSEA. The signature indicated decreased purity of the tumor by implying a lower proportion of cancer cells along with an increasing enrichment of fibroblasts, myeloid dendritic cells, and monocytic lineage cells.
Our research suggests that the immune-related lncRNA signature possesses latent prognostic value for patients with pancreatic cancer and may provide new information for immunological research and treatment in pancreatic cancer.
鉴定具有潜在预后价值的胰腺癌免疫相关长非编码 RNA（lncRNA）特征。
本研究纳入了具有可用临床信息和全基因组 mRNA 表达数据的胰腺癌样本，这些数据来自癌症基因组图谱（TCGA）。根据免疫相关基因的表达水平计算每个样本的免疫评分，并用于鉴定最有前途的免疫相关 lncRNA。根据筛选出的免疫相关 lncRNA 开发的风险评分，根据中位数风险评分将高风险组和低风险组分开。在验证集和组合集中进一步评估预测可靠性。进行基因集富集分析（GSEA）和主成分分析（PCA）进行功能注释，并应用微环境细胞群体记录评估肿瘤的免疫组成和纯度。
本研究纳入了 176 例样本。根据免疫评分与 lncRNA 表达之间的 Pearson 相关分析（|R|>0.5，P<0.01），共收集了 163 个免疫相关 lncRNA。鉴定出 9 个具有最显著预后价值的免疫相关 lncRNA（AL138966.2、AL133520.1、AC142472.1、AC127024.5、AC116913.1、AC083880.5、AC124016.1、AC008443.5 和 AC092171.5）（P<0.01）。在训练集中，低风险组患者的总生存期（OS）长于高风险组（P<0.001）；同时，在验证集、组合集和各种分层集（P<0.05、P<0.001、P<0.05）中也发现了类似的结果。此外，该特征被确定为独立的预后因素，与胰腺癌的 OS 显著相关。9 个 lncRNA 特征预测 2 年生存率的受试者工作特征曲线（ROC 曲线）的 AUC 为 0.703。此外，低风险和高风险组在 PCA 中显示出不同的分布模式，在 GSEA 中显示出不同的免疫状态。该特征表明肿瘤纯度降低，表明癌细胞比例降低，同时成纤维细胞、髓样树突状细胞和单核细胞谱系细胞的富集增加。
本研究表明，免疫相关 lncRNA 特征对胰腺癌患者具有潜在的预后价值，可为胰腺癌的免疫研究和治疗提供新的信息。
